Funds are requested to purchase a high field ultra-shielded MHz magnetic resonance (NMR) spectrometer equipped with a cryoprobe. This instrument will be housed at the Cleveland Center for Structural Biology (CCSB) to serve students, postdoctoral fellows, research faculty of Case Western Reserve University (CWRU), the Lerner Research Institute of the Cleveland Clinic Foundation (CCF), and Cleveland State University (CSU). The current proposal is aimed at acquiring a state-of- the-art instrument that will support the current NIH-funded research project of about twenty scientists and researchers that make up the CCSB. The faculty associated with CCSB has doubled in the past two years with the hiring of six new full-time structural biologists to both CWRU and CCF, among which five carry our extensive NMR studies of biomolecules. These new research groups and the existing structural biology faculty together with their collaborators on NIH-funded research total more than 100 users of the current three machines dedicated to biomolecular studies. Most of the investigators have to travel to neighboring cities to carry out their research. It is also common to wait for 3 weeks before getting on the current 600 MHz machines, and the situation will only worsen as the new recruits launch vigorously into their research programs. The current instrumentation (two 600, one 500, and one 300 MHz spectrometers) is woefully inadequate to meet the current demands of the structural community in Cleveland. The ultra-shielded studies being carried out here in Cleveland Most of these are disease- oriented structural biology projects. Increasing the number of and access to state-of-the-art NMR spectrometers with a cryoprobe will not only relieve the over-use of current machines, but more importantly (1) spur the development of new NMR techniques to push forward current and future structural projects to aid rational drug design, and (2) play a direct role in on-going graduate student and postdoctoral training in structural biology. It will not only make an impact on research projects of Cleveland structural biology community but also create an active core of NMR structural biology experts trained in the most current and sophisticated techniques.